Three fMRI CPT codes (for clinical billing and insurance) have been approved and went into effect January 1, 2007. Clinical fMRI will expand rapidly. However, clinical fMRI is often confounded by excessive patient motion. Studies are lost and subjects need to be recalled. Moreover, during the fMRI scan, patients must adequately perform a behavioral task, which can suffer if they become fatigued or fall asleep. Functional MRI studies often take too long. These two problems-patient motion/performance and scan-session length-are the focus of this proposal. Improved methodology is the goal. The three aims address the problems from different perspectives: Aim 1: Pulse sequences and imaging physics for separation of fMRI signals from motion artifacts;Aim 2: Real-time statistics and image analysis for shortening scan duration and improvement of noise immunity;Aim 3: Management of scan-session duration with adaptive acquisition paradigms, multi-parameter mapping, and real-time clinically relevant displays. The aims come together in multifaceted interactive attacks on the two problems. Motion-contaminated data will either be fixed in real time or censored in real time accompanied by additional data acquisition. On a voxel-by-voxel basis, adaptive Kalman filtering will adjust baseline variation caused by slow-motion drift. Higher receiver bandwidth can reduce motion artifacts in several ways. We will explore use of receiver bandwidths as high as 1 MHz, with correspondingly higher gradient strengths. At its essence, this is a study of physiological noise relative to scanner preamplifier noise. As for scan-session length, studies should not extend longer than necessary for statistically significant results, which requires real-time statistical analysis. Randomized multiplexed behavioral paradigms reduce test time. In addition, all of the foregoing techniques will be implemented in near-real time through the use of increased computer power in the MRI scanner suite. In the end, we seek a clinically relevant determination of scan-session success before the patient leaves the scanner, allowing fMRI to be used in a conventional test/retest paradigm. This will significantly improve the success rate of fMRI exams and thereby facilitate the adoption of fMRI as a routine clinical tool. Research will be performed on a GE 3T scanner that was purchased in 2005 using funds made available through the High End Instrumentation Program of the National Center for Research Resources. The work will be carried out by one of the pioneering groups in fMRI. The potential impact of fMRI on brain-related disease is enormous. References are made in the proposal to two specific studies underway at the Medical College of Wisconsin: subjects with mild cognitive impairment that may lead to Alzheimer's disease, and fMRI mapping of visual, motor, and speech function prior to surgical treatment of brain tumors. There are many more.